Acute and Subchronic Neurotoxicity Studies with Tri-n-butyl Phosphate in Adult Sprague-Dawley Rats

Abstract

Male and female adult Sprague-Dawley rats received tributyl phosphate (TBP) in corn oil by gavage in acute (single-dose) and subchronic (three-month) studies. Dosage levels in the acute study were 100, 325, and 1000 mg/kg; they were 32.5, 100, and 325 mg/kg/day in the subchronic study. Behavioral evaluations were performed in both studies, and neuropathological evaluations were performed in the three-month study only. The methods used in the studies are as described in the U.S. Environmental Protection Agency neurotoxicity guidelines. Mean body weight decreases were statistically significant compared to controls for male rats at the high-dosage level only in the acute study. Transient changes only, attributable to the general toxicity of the material, were noted in forelimb grip strength and mean activity level during the first 24 hours after dosing for 1000 mg/kg rats. In the subchronic study high-dose males and females had statistically significant body weight decreases; some mortality also was observed at this dosage level. The motor activity levels and qualitative and quantitative functional observational battery measurements were comparable between treatment and control groups, and there were no gross or neurohistopathological findings in the rats indicative of treatment-related effects. Based on these study results, TBP was not neurotoxic to rats following either acute or subchronic exposures.